Does the preferred orientation of crystallites in tablets affect the intrinsic dissolution?

Abstract

The aim of this study was to examine the effect of preferred orientation of crystallites, i.e. texture, on the intrinsic dissolution rate of some active pharmaceutical ingredients. Although it has often been speculated that the intrinsic dissolution of pharmaceutical tablets is affected by texture, no experimental evidence of this effect has been reported. The texture of acetylsalicylic acid, tolbutamide, carbamazepine and entacapone tablets was measured using three different methods both before and after the dissolution measurements. To clarify the effect of texture, texturizing and less-texturizing batches of each material were used. The texturizing batches had big needle or plate-like particles and the less-texturizing batches were prepared by grinding the texturizing powders. The USP rotation disc method was used to measure the intrinsic dissolution rate of the samples. The results indicated that the acetylsalicylic acid, tolbutamide and entacapone tablets texturized strongly in compression and the grinding of the texturizing powders decreased the degree of texture. Also the carbamazepine tablets were slightly texturized. All of the texture measurement methods used were found to give acceptable and consistent results and therefore a special texture goniometer is not required to perform these measurements. The intrinsic dissolution rate of all the tablets compacted from the ground powder was slightly higher than the intrinsic dissolution rate of the more texturized samples. However, these differences were not significant on a large scale. After the dissolution tests the degree of texture of the samples was decreased. The intrinsic dissolution rates of the samples were presumably affected by several different parameters such as texture, solubility, pH, surface energetics and crystal strains. Although only small differences were found between the intrinsic dissolution rates of texturized and less texturized samples the effect of texture on the dissolution behavior of the pharmaceuticals should be considered when performing accurate intrinsic dissolution studies.